rs2274623

Variant names:

• chr1-179550973-C-T
• rs2274623
• NM_014625.4:c.*200G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-179550973-C-T
• chr1-179550973-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014625.4(NPHS2):​c.*200G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 652,868 control chromosomes in the GnomAD database, including 14,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2489 hom., cov: 32)
  • Exomes 𝑓: 0.21 (11990 hom.)
• Consequence: NPHS2 NM_014625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.117
• Publications: 8 publications found

Genes affected

NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

AXDND1 (HGNC:26564): (axonemal dynein light chain domain containing 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-179550973-C-T is Benign according to our data. Variant chr1-179550973-C-T is described in ClinVar as Benign. ClinVar VariationId is 224484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHS2	NM_014625.4	MANE Select	c.*200G>A		3_prime_UTR	Exon 8 of 8	NP_055440.1	Q9NP85-1
	AXDND1	NM_144696.6	MANE Select	c.3032-3539C>T		intron	N/A	NP_653297.3
	NPHS2	NM_001297575.2		c.*200G>A		3_prime_UTR	Exon 7 of 7	NP_001284504.1	Q9NP85-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHS2	ENST00000367615.9	TSL:1 MANE Select	c.*200G>A		3_prime_UTR	Exon 8 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.*200G>A		3_prime_UTR	Exon 7 of 7	ENSP00000356588.4	Q9NP85-2
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-3539C>T		intron	N/A	ENSP00000356590.3	Q5T1B0-1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24595 AN: 152054 Hom.: 2494 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.211 AC: 105822 AN: 500696 Hom.: 11990 Cov.: 6 AF XY: 0.214 AC XY: 56587 AN XY: 264270

African (AFR) AF: 0.0398 AC: 546 AN: 13702

American (AMR) AF: 0.226 AC: 5238 AN: 23190

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 2470 AN: 14704

East Asian (EAS) AF: 0.354 AC: 10850 AN: 30692

South Asian (SAS) AF: 0.257 AC: 12503 AN: 48700

European-Finnish (FIN) AF: 0.187 AC: 5425 AN: 28946

Middle Eastern (MID) AF: 0.170 AC: 355 AN: 2092

European-Non Finnish (NFE) AF: 0.203 AC: 63133 AN: 311018

Other (OTH) AF: 0.192 AC: 5302 AN: 27652

GnomAD4 genome AF: 0.162 AC: 24586 AN: 152172 Hom.: 2489 Cov.: 32 AF XY: 0.165 AC XY: 12278 AN XY: 74370

African (AFR) AF: 0.0411 AC: 1707 AN: 41546

American (AMR) AF: 0.202 AC: 3086 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1795 AN: 5182

South Asian (SAS) AF: 0.265 AC: 1274 AN: 4816

European-Finnish (FIN) AF: 0.177 AC: 1870 AN: 10566

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13780 AN: 67996

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.185 Hom.: 9704

Bravo AF: 0.157

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Nephrotic syndrome, type 2 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2274623; hg19: chr1-179520108;